Device for introducing a liquid into a pharmaceutical container

ABSTRACT

An apparatus for introducing a liquid into a pharmaceutical container such as a vial, having a puncturable closure, comprising a hollow needle with at least one orifice through the needle side wall being oriented to direct liquid flowing along the bore in a direction having a component parallel to the flow direction, with a vent groove in its outer surface. A preferred construction of needle and a process for making it are disclosed.

This invention relates to an apparatus for use in filling pharmaceuticalvials which have an elastomeric closure which can be punctured by aneedle point and fluid medicament content thereby introduced into thevial.

Such a process is known from US-A-2002/0023409 in which the residualpuncture site left by the needle is heat sealed using a laser beam.

Needles for this purpose are known, but a problem with such needles isthat of achieving an optimised flow pattern of the fluid as it exits theneedle when within the vial. A further problem is that the point andside orifices of known needles can cut through the vial closure duringpuncture in a way which forms particles of the closure material whichcan contaminate the medicament introduced into the vial or block orobstruct flow through the needle.

There are numerous disclosures of hollow, pointed ended needles havingside orifices for the exit of fluid. For example U.S. Pat. No. 5,478,328and U.S. Pat. No. 6,221,056 disclose needles in which the side orificesare profiled to direct a fluid flowing along the bore of the needle andout through the orifices forwards, i.e. in the direction in which theneedle is pointing. The needles disclosed therein are not disclosed orsuggested for use in a vial filling operation.

It is an object of this invention to provide an improved vial fillingapparatus based on improved needles, addressing these problems amongothers. Other objects and advantages of this invention will becomeapparent from the following description.

According to this invention an apparatus for introducing a liquid into apharmaceutical container having a puncturable closure is provided,comprising;

a hollow needle suitable for passing through the closure, the needlecomprising a tubular conduit defined by a side wall and having aninternal bore for the flow of a fluid along the bore in a flowdirection, the conduit terminating externally at a pointed end, the boreterminating internally at a closed end, at least one orifice through theside wall for the exit of fluid flowing along the bore, the at least oneorifice being oriented to direct liquid flowing along the bore in adirection having a component parallel to the flow, the conduit having atleast one vent groove in its outer surface;

means to cause the needle to puncture the closure to the extent that theat least one orifice is within the container;

means to cause the liquid to flow along the bore;

means to withdraw the needle from the container and closure.

The orientation of the orifice to direct liquid flowing along the borein a direction having a component parallel to the flow direction may beachieved by an orifice which has a perimeter surface through the sidewall converging toward the upstream direction so as to direct a flow offluid passing through the orifice from the bore toward the outside ofthe needle in a direction which has a component in the downstreamdirection.

Herein the term “downstream” refers to the general direction between theend of the needle into which fluid is introduced and the pointed end,and “upstream” refers to the opposite direction.

The benefit of such an alignment of the perimeter surfaces of the boreis that fluid exiting through the orifice is thereby directed in thedownstream direction, rather than exiting substantially perpendicularlyto the downstream direction.

Preferably the conduit is cylindrical and there are two orifices withtheir centres 180° apart i.e. on opposite sides of a diameter of theconduit.

Preferably the orifice(s) is(are) elongate in the longitudinal directionof the conduit, for example being oval.

Preferably the total cross sectional area of the one or more orifice issubstantially the same +/−20% as the cross sectional area of the bore ofthe conduit so that flow of fluid out through the orifice(s) from thebore is not restricted.

Preferably the orifice has an upstream perimeter surface through theside wall inclined to converge toward the upstream direction. Preferablythe orifice has a downstream perimeter surface through the side wallinclined to converge toward the upstream direction. If both upstream anddownstream perimeter surfaces are inclined to converge with the upstreamdirection they may incline parallel to each other. Preferably the angleof convergence toward the upstream direction of the upstream and ifpresent downstream perimeter surface of the orifice is at an angle of10-60°, more preferably ca. 30°, with the upstream direction.

Preferably the perimeter of the orifice is rounded rather than sharp toreduce the possibility of cutting of the closure by sharp edges of theorifices as they pass through an elastomer vial closure, and theconsequent formation of particles of the closure material.

Preferably the internal closed end of the bore comprises surfaces thatconverge toward the upstream direction.

Preferably these surfaces converge toward the upstream direction in theform of an edge with its ridge pointing in the upstream direction, beingmore preferably a sharp knife edge between the surfaces of the closedend. Preferably the angle of convergence is the same as that of one ormore of the converging perimeter surfaces of the orifice.

Preferably if there are two orifices the edge formed by these convergingsurfaces of the internal closed end of the bore is aligned with the lineof its ridge perpendicular to the axis between the two orifices. Thesloping alignment of these surfaces of the edge is preferably the sameas that of the upstream perimeter surface of the orifice, i.e. at theangles disclosed above, and preferably merges smoothly with theperimeter of the orifice.

Preferably the converging surfaces of the internal closed end of thebore, e.g. the ridge of a so-formed edge, extend in the upstreamdirection at least as far as the upstream perimeter of the orifice. Theedge is preferably part of a so called “saddle” shaped surface.

The advantage of such converging internal surfaces, particularly thisedge, is that flow of fluid exiting from the orifice is guided therebyin the downstream direction, and such an edge, e.g. in the form of asaddle shaped surface provides no flat surface for particles or othercontamination to rest upon.

The pointed end may be a pyramid with three faces. The apex of such apyramid may enclose an angle of 30-60°. Preferably the pointed end is aconical shape, suitably having a cone angle of 15-30°, preferably20-25°, at the pointed tip. The benefit of a cone shape over a pyramidalshape is that the conical shape damages less of the elastomer materialas it punctures the closure, whereas a pyramid can leave a larger “star”shaped puncture hole with cuts radiating from the apexes of thepolygonal e.g. triangular, section of the pyramid. Such a cone shape cangenerate no particles of the closure material is it punctures theclosure.

Therefore a specific preferred form of the needle for the apparatus ofthis invention comprises:

a cylindrical tubular conduit defined by a side wall and having aninternal bore for the flow of a fluid along the bore in an flowdirection, the conduit terminating externally at a conically pointedend, the bore terminating internally at a closed end, at least oneorifice through the side wall for the exit of fluid flowing along thebore,

wherein at least one orifice has upstream and downstream perimetersurfaces through the side wall converging toward the upstream directionat an angle between 10-60° relative to the upstream direction,

the total cross sectional area of the one or more orifice is +/−20% ofthe cross sectional area of the bore of the conduit,

and the internal closed end of the bore comprises surfaces that convergetoward the upstream direction.

Preferably the pointed end of the conduit is provided as a separate plugpart which can be plugged into the downstream open end of the conduit.Such a plug part may consequently comprise a male plug end which can beinserted into the open downstream end of the bore of a tubular conduit,the plug part having a pointed end longitudinally opposite this maleplug end, the plug end being shaped into the above-described edge. Sucha plug end may be welded into the bore of the conduit.

The conduit is also provided on its external surface with one or morevent groove to allow the atmosphere within a container such as a vial toescape as fluid is introduced into the container. Suitably such a groovemay extend in a direction parallel to the longitudinal axis of theconduit, e.g. parallel to the upstream-downstream direction. The lengthof such a groove need be sufficient that when the needle has puncturedthe closure to its fully intended extent one end of the groove is withinthe container and the other end is exposed outside of the container.There may be one or more such vent groove, preferably two or more ventgrooves. It is found that the venting efficiency can influence the vialfilling speed, and four grooves can be better for filling larger volumevials. It is found that when the needle is used to puncture an elastomerclosure, e.g. of a vial, the elastomer tends to fill the vent groove(s).It is found that this can be avoided by a groove which is of a profile,cut across the axis of the needle, which has sharp corners, which arenot easily completely filled by the elastomer. For example the groovemay have a rectangular profile. Plural grooves may be regularly spacedaround the circumference of the conduit. An alternative arrangement isfour grooves arranged in two pairs, each pair disposed on opposite sidesof a diameter of the conduit, grooves in each pair, with a 20-50°, e.g.40 ±5° angular spacing between the grooves of the pair. The groove mayfor example have a depth of ca. 50% of the thickness of the conduitwall, e.g. 0.2 mm deep, and a width 0.2-0.4 mm. It is preferred that atthe ends of the groove(s) the groove accomodates gradually to the outerprofile of the conduit, rather than at a sharp step, to avoid cuttingparticles of the elastomer of the closure on insertion or removal of theneedle through the closure. Needles having these dispositions of ventgrooves are believed to be novel.

The above-mentioned guiding of the flow of fluid exiting from the boreinto the downstream direction has a further advantage in reducing thepossibility of the fluid being sprayed in the upstream direction andentering the vent groove.

The conduit and plug part as described above may be made of metals suchas stainless steel as commonly used in the art. Typically the conduitmay have an outside diameter ca. 2-3 mm, and the bore may have aninternal diameter 1-2 mm, with a side wall thickness typically 0.3-0.5mm.

The container may suitably be a pharmaceutical vial having a puncturableelastomeric closure. Suitable vials are disclosed for example in WO04/018317. Such a vial for example has an upwardly-facing mouth openingbounded by a rim in the form of a flange having upper and lower surfacesextending transverse to its upper-lower axis, and has an elastomerclosure part shaped to sealingly engage with the mouth opening, having alower surface to face the interior of the vial and an opposite uppersurface to face away from the vial, and capable of being punctured by aneedle is inserted into the mouth opening of the vial, and has a clamppart engaged with the flange around the rim of the mouth opening of thevial by a resilient snap-fit engagement of a snap fit part of the clamppart underneath a downwardly facing surface of such a flange part, andbearing upon the upper surface of the closure part to hold the closurepart in a closing relationship with the mouth opening.

The means to cause the needle to puncture the closure may comprise meansto hold the needle and support the container, e.g. a vial, and causethem to move relatively together along the longitudinal axis of theneedle. For example the container may be a vial supported with itsclosure uppermost, and the needle may be held above the container andmoved downwardly toward the closure. Suitably the container such as avial may be supported on a conveyor below the needle holder. The meansto withdraw the needle from the container and closure may comprise thesame means but operating in a reverse reciprocal movement. The means tosupport the container, particularly a vial, should incorporate means torestrain the container against the withdrawing force of the needle. Asuitable means is for example disclosed in WO-A-04/026735. For examplethe vial may have a bottom opposite its mouth opening which fits into avial stand, and this means may bear upon the stand to hold thecombination of vial and stand down against the withdrawing force.

The means to cause the liquid to flow along the bore may comprise aconventional metering pump connected to a supply of the liquid. Such apump may be operated to deliver a metered amount of the liquid into thecontainer, and may be controlled to that the liquid is only deliveredwhilst the orifice is within the container. In another aspect theinvention provides a process for making a hollow needle as describedabove comprising the steps of:

(1) providing a tubular conduit defined by a side wall and having aninternal bore for the flow of a fluid along the bore in an flowdirection, the bore having an open end;

(2) providing a plug part for the open end, the plug part having alongitudinal axis and being adapted to longitudinally mate with the openend of the bore and having an end surface and an opposite end,

(3) mating the plug part longitudinally with the bore,

(4) cutting at least one orifice through the side wall in a directionconverging toward the upstream direction and forming the end surface ofthe plug part into side surfaces that converge toward the upstreamdirection,

(5) before or after any of steps (1) to (4) forming the opposite end ofthe plug part into a point.

Preferably prior to step (3) the end surface of the plug part is formede.g. cut into the shape of a valley with its bottom extending across theend surface perpendicular to the longitudinal direction, preferably a“V” or “U” sectioned valley.

In step (4) the orifice is cut e.g. by drilling from a directionparallel to the line of the bottom of the valley. Cutting in thispreferred way can form the above mentioned saddle shaped closed endsurface of the bore.

Preferred features of the so-made needle are as disclosed above.

For example in step (3) the plug part may be welded e.g. laser welded tothe conduit side wall when in place in the bore. Preferably after beingmade as described above the outer surface of the needle is polished,e.g. electropolished, to remove burrs but not to produce a surface thatis so smooth that there is high friction between the needle and a vialclosure which it punctures.

The vent groove(s) may be made in the outer surface of the conduit atany stage in the above needle-making process. The vent groove(s) may bemade using a milling tool which penetrates the outer surface of theconduit progressively.

In another aspect the invention provides a process for introducing afluid into a puncturable container comprising the steps of;

(1) inserting the point of a needle as described above into the interiorof the container by puncturing the container,

(2) flowing a fluid along the bore of the needle in the flow direction,

(3) causing the fluid to exit the needle through the one or more orificeand thereby enter the container, then

(4) withdrawing the needle from the container.

For example the container may be a pharmaceutical vial having apuncturable closure and the fluid may be a liquid medicament.

The invention will now be described by way of example only withreference to the accompanying drawings.

FIG. 1 shows a longitudinal and cross section through the pointed end ofa needle of this invention.

FIG. 2 shows sequentially a process for making the needle of FIG. 1.

Referring to FIG. 1 the end of a needle 10 (overall) adjacent to thepoint 11 is shown. Needle 10 comprises a cylindrical tubular conduit 12made of stainless steel of circular section of outside diameter 2.4 mmdefined by a side wall 13 and having an internal circular sectioned bore14 of inside diameter 1.65 mm, the thickness of the side wall 13 being0.38 mm. The conduit 12 is suitable for the flow of a fluid (not shown)along the bore 14 in an flow direction indicated by the arrow.

Externally the conduit terminates externally at pointed end 11, which isin shape a cone with a cone angle at its apex of ca. 20-45°. Such aconical profile avoids sharp cutting edges which could form particles ofelastomer material as the point punctures an elastomer closure.

There are two orifices 15 through the side wall 13 for the exit of fluidflowing along the bore 14. These orifices are located 180° apart, i.e.diametrically opposite each other on opposite sides of the bore 14. Eachorifice 15 is of an oval shape elongated parallel to theupstream-downstream direction. Each of the orifices 15 has an upstreamperimeter surface 15A and also a downstream perimeter surface 15Bthrough the side wall 13 converging toward the upstream direction at anangle (A) of ca. 30° with the upstream direction, i.e. parallel to theupstream surface 15A.

The edge 15C of the upstream perimeter surface 15A is rounded to reduceany possibility of the edge 15C cutting material of a closure throughwhich the needle is passed. The total cross sectional area of the twoorifices 15, i.e. at the extrapolated inner surface of the bore 14 issubstantially the same as the cross sectional area of the bore 14.

The bore 14 terminates at a closed end 16 which is profiled. This closedend 16 of the bore comprises surfaces 17 that converge toward theupstream direction, and which meet at a sharp knife edge ridge 18. Theorientation of the line of the edge 18 is perpendicular to the axisbetween the two orifices 15, i.e. aligned with a diameter at 90° to thediameter on which are located the orifices 15. The sloping surfaces 17consequently are intersected by the same diameter that passes throughthe orifices 15. As is seen in FIG. 1 the sloping alignment of the sidesurfaces 17 of the edge 18 is the same as that of the downstreamperimeter surfaces 15B of the orifices 15 so that the surfaces 17 mergesmoothly with the perimeter surface 15B of the orifice 15. The edge 18extends in the upstream direction beyond the upstream perimeter 15A ofthe orifice.

The pointed end 11 is provided as a separate plug part 20 which can beplugged into the downstream open end 21 of the bore. Plug part 20comprises a male plug end 22 which can be inserted into the opendownstream end 21 of the bore 14 of the tubular conduit 12 and has anopposite pointed end part 23 comprising the point 11, the plug end 22being shaped into the above-described edge 18 with its sloping sidesurfaces 17.

The conduit 12 is also provided externally with two diametricallyopposite vent grooves 24, each ca. 0.2 mm deep, visible in FIG. 2. Thelongitudinal ends 24A of each groove 24 accomodates gradually to theouter profile of the conduit 12, rather than with a sharp step.

It will be apparent that fluid flowing along bore 14 will be directedinto a direction having a component in the downstream direction uponexiting through the orifices 15, because of the directing effect of thefluid guide surfaces 15A, 15B, 17.

FIG. 1A shows a cross section through the conduit 12 of the needle 10 ofFIG. 1 at the line A-A of FIG. 1. The two vent grooves 24 more clearlyseen in FIG. 2 can be seen situated 180° apart around the outercircumference of the conduit 12. FIG. 1B shows an alternative crosssection through the conduit 12 of the needle 10 of FIG. 1 at the lineA-A of FIG. 1. The two vent grooves 24 more clearly seen in FIG. 2 canbe seen situated 180° apart around the outer circumference of theconduit 12. The thickness of the steel wall of the conduit 12 is ca.0.38 mm. The two vent grooves 24 each have a width of ca. 0.4 mm and adepth of ca. 0.2 mm. FIG. 1C shows another alternative cross sectionthrough the conduit 12 of the needle 10 of FIG. 1 at the line A-A ofFIG. 1. Four vent grooves 24 are seen, disposed in two pairs situated1800 apart across a diameter of conduit 12. The grooves 24 of each pairare spaced ca. 40° apart around the outer circumference of the conduit12. The thickness of the steel wall of the conduit 12 is ca. 0.40 mm,the conduit diameter being 2.4 mm. The four vent grooves 24 each have awidth of ca. 0.2 mm and a depth of ca. 0.2 mm. In FIGS. 1B and 1C theedge between the sides of the groove 24 and the outer surface of conduit12 is radiused at ca. 0.05 mm to avoid cutting particles of a closure asthe needle punctures the closure.

Referring to FIG. 2 a process for making the needle of FIG. 1 is shownsequentially.

Referring to FIG. 2A step (2) of the above-described process is shown. Aplug part 30 for the open end of the bore 14 of a conduit is shown. Theplug part 30 is elongated along the vertical longitudinal axis. One end31 is formed into a male plug adapted to longitudinally mate with theopen end 21 of the bore of a conduit, i.e. being of an outside diametercorresponding to the internal diameter of the open end 21 of the bore 14so that end 31 is a tight fit in open end 21. The opposite end 32 isformed into a pyramidal point. The end surface 31 of the plug part 30has been cut into the shape of a “V” sectioned valley 33 with its bottomextending across the end surface 31 in the direction B-B perpendicularto the longitudinal direction. There is an abutment ledge 34 around thepart of the plug part 31 closest to the point 32 to limit the extent towhich the part 31 can enter the bore 14.

As seen in FIG. 2B the plug part 30 has been mated with the open end ofthe tubular conduit 12, i.e. step (3).

FIG. 2C shows step (4). Two orifices 15 have been drilled atdiametrically opposite positions through the side wall 13 of conduit 12in a direction converging toward the upstream direction. The line B-B ofthe bottom of the valley 33 is aligned parallel to the diameter of theconduit joining the two orifices 15. The downstream perimeter surface15B of orifice 15 is visible.

FIG. 2D shows the rounding of the upstream perimeter surfaces 15A of theorifices 15 using a tool 35, to form the rounded edge 15C.

FIG. 2E shows in an exploded view how the drilling of the orifices 15through the side wall 13 has formed the end surface 16 of the plug end22 of plug part 20 into side surfaces 17 that converge toward theupstream direction to form the edge 18, and which form part of anoverall “saddle” shaped surface, i.e. with surfaces 19 inclined relativeto the upstream-downstream direction and generally in planesperpendicular to the planes of the side surfaces 17.

FIG. 3 shows how the needle of FIG. 1 is used in an apparatus of theinvention. As seen in FIG. 3A a pharmaceutical vial 31 is providedhaving a puncturable elastomer closure 32, held in place in a closingrelationship with the mouth of the vial 31 by a clap part 33 which has acentral aperture 34 through which the closure 32 is exposed. Theinterior of vial 31 and the part of closure 32 exposed within aperture34 have been pre-sterilised.

A hollow needle 35 of the type shown and described with reference toFIGS. 1 and 2 is supported above vial 32, with its point downwards andaimed at closure 32 through aperture 34. Needle 35 is supported byholder 36 which can be moved reciprocally upwardly and downwardlyrelative to vial 31 by suitable means (not shown). Holder 36 alsoconnects needle 35 to a source (not shown) of a liquid via line 37.

Vial 31 has its bottom held by a base 38 which enable vial 31 to be helddown onto a conveyor (not shown) by which vial 31 may be movedunderneath needle 35 into the relationship shown.

As seen in FIG. 3B, the needle 35 has been moved downwardly by means ofa corresponding downward movement of holder 36, so that needle 35punctures and passes through the closure 32 with orifices shown 15 inFIGS. 1 and 2 within vial 31.

As seen in FIG. 3C, a liquid 39 is caused to flow along line 37 throughconduit 12 (as seen in FIGS. 1 and 2) of the needle 35, to exit via theorifices 15 into vial 31. The orientation of the orifices 15 directs theliquid 39 to flow out of the needle 35 in a direction having a componentparallel to the flow direction, i.e. having a downward component as seenin FIG. 3C. The flow of liquid 39 is seen to be in a direction at anon-zero, non-perpendicular direction to the longitudinal axis of theneedle 35. Flowing in this direction the liquid 39 is directed away fromthe underside of closure 32 and the upper regions of the interior ofvial 31 toward the bottom of vial 31. The vent groove shown 24 in FIG. 2in the outer surface of needle 35 has a length sufficient that when theneedle 35 has punctured the closure 32 to its fully intended extent asseen in FIG. 3C one end of the groove 24 is within the vial 31 and theother end is exposed outside of the vial, so that air within the vial 31can escape via the groove 24 as shown 310.

As seen in FIG. 3D a reciprocal upward movement of the holder 36 andneedle 35 has caused the needle 35 to be withdrawn from the vial 31 andclosure 32. The vial 31 may be held down by a holding means (not shown)applied to the base 38. The residual puncture hole 311 may be heatsealed.

The entire operation shown in FIGS. 3A-3D is preferably performed undera downward laminar flow of sterilised air (not shown).

1. Apparatus for introducing a liquid into a pharmaceutical containerhaving a puncturable closure, comprising; a hollow needle suitable forpassing through the closure, the needle comprising a tubular conduitdefined by a side wall and having an internal bore for the flow of afluid along the bore in an flow direction, the conduit terminatingexternally at a pointed end, the bore terminating internally at a closedend, at least one orifice through the side wall for the exit of fluidflowing along the bore, the at least one orifice being oriented todirect liquid flowing along the bore in a direction having a componentparallel to the flow direction, the conduit having at least one ventgroove in its outer surface; means to cause the needle to puncture theclosure to the extent that the at least one orifice is within thecontainer; means to cause the liquid to flow along the bore; means towithdraw the needle from the container and closure.flow
 2. Apparatusaccording to claim 1 comprising means to hold the needle and support thecontainer, and to cause them to move relatively together along thelongitudinal axis of the needle.
 3. Apparatus according to claim 3wherein the container is a vial supported with its closure uppermost,and the needle is held above the container and moved downwardly towardthe closure.
 4. Apparatus according to claim 2 wherein the container issupported on a conveyor below the needle holder.
 5. Apparatus accordingto claim 2 wherein the means to withdraw the needle from the containerand closure comprises the means to hold the needle and support thecontainer, operating in a reverse reciprocal movement.
 6. Apparatusaccording to claim 2 wherein the means to support the containerincorporates means to restrain the container against the withdrawingforce of the needle.
 7. A hollow needle comprising a tubular conduitdefined by a side wall and having an internal bore for the flow of afluid along the bore in an flow direction, the conduit terminatingexternally at a pointed end, the bore terminating internally at a closedend, at least one orifice through the side wall for the exit of fluidflowing along the bore, the at least one orifice being oriented todirect liquid flowing along the bore in a direction having a componentparallel to the flow direction, the conduit having at least one ventgroove in its outer surface and wherein the pointed end of the conduitis provided as a separate plug part which can be plugged into thedownstream open end of the conduit.
 8. A needle according to claim 3which comprises: a cylindrical tubular conduit defined by a side walland having an internal bore for the flow of a fluid along the bore in anflow direction, the conduit terminating externally at a pointed end, thebore terminating internally at a closed end, at least one orificethrough the side wall for the exit of fluid flowing along the bore,wherein at least one orifice has upstream and downstream perimetersurfaces through the side wall converging toward the upstream directionat an angle between 10-60° relative to the upstream direction, the totalcross sectional area of the one or more orifice is +/−20% of the crosssectional area of the bore of the conduit, and the internal closed endof the bore comprises surfaces that converge toward the upstreamdirection.
 9. A process for making a hollow needle according to claim 2comprising the steps of: (1) providing a tubular conduit defined by aside wall and having an internal bore for the flow of a fluid along thebore in an flow direction, the bore having an open end; (2) providing aplug part for the open end, the plug part having a longitudinal axis andbeing adapted to longitudinally mate with the open end of the bore andhaving an end surface and an opposite end, (3) mating the plug partlongitudinally with the bore, (4) cutting at least one orifice throughthe side wall in a direction converging toward the upstream direction,and forming the end surface of the plug part into side surfaces thatconverge toward the upstream direction, (5) before or after any of steps(1) to (4) forming the opposite end of the plug part into a point.
 10. Aprocess according to claim 9 wherein prior to step (3) the end surfaceof the plug part is formed into the shape of a valley with its bottomextending across the end surface perpendicular to the longitudinaldirection.
 11. A process according to claim 9 wherein in step (4) theorifice is cut by drilling from a direction parallel to the line of thebottom of the valley.
 12. A process for introducing a fluid into apuncturable container comprising the use of an apparatus according toclaim 1 to perform the steps of; (1) inserting the point of the needleinto the interior of the container by puncturing the container, (2)flowing a fluid along the bore of the needle in the flow direction, (3)causing the fluid to exit the needle through the one or more orifice andthereby enter the container, then (4) withdrawing the needle from thecontainer.
 13. A process for introducing a fluid into a puncturablecontainer comprising the steps of; (1) inserting the point of a needleas claimed in claim 7 into the interior of the container by puncturingthe container, (2) flowing a fluid along the bore of the needle in theflow direction, (3) causing the fluid to exit the needle through the oneor more orifice and thereby enter the container, then (4) withdrawingthe needle from the container.
 14. A process according to claim 13wherein the container is a pharmaceutical vial having a puncturableclosure.
 15. A process for introducing a fluid into a puncturablecontainer comprising the steps of; (1) inserting the point of a needleas claimed in claim 8 into the interior of the container by puncturingthe container, (2) flowing a fluid along the bore of the needle in theflow direction, (3) causing the fluid to exit the needle through the oneor more orifice and thereby enter the container, then (4) withdrawingthe needle from the container.
 16. A process according to claim 15wherein the container is a pharmaceutical vial having a puncturableclosure.